CA2171336A1 - Recombinant il4 antibodies useful in treatment of il4 mediated disorders - Google Patents
Recombinant il4 antibodies useful in treatment of il4 mediated disordersInfo
- Publication number
- CA2171336A1 CA2171336A1 CA002171336A CA2171336A CA2171336A1 CA 2171336 A1 CA2171336 A1 CA 2171336A1 CA 002171336 A CA002171336 A CA 002171336A CA 2171336 A CA2171336 A CA 2171336A CA 2171336 A1 CA2171336 A1 CA 2171336A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- human
- acid sequence
- nucleic acid
- gat
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
- C07K16/247—IL-4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Abstract
Chimeric and humanized IL4 MAbs derived from high affinity MAbs, pharmaceutical compositions containing same, and methods of treatment are provided.
Claims (38)
1. A fusion protein having binding specificity for human interleukin-4 (IL4) which comprises complementarity determining regions (CDRs) derived from a non-human neutralizing monoclonal antibody characterized by a dissociation constant equal to or less than 2 x 10-10 M for human IL4, and a first fusion partner.
2. The fusion protein according to claim 1 which is operatively linked to a second fusion partner.
3. The fusion protein according to claim 1 wherein said non-human neutralizing monoclonal antibody is selected from the group consisting of 3B9 and 6A1.
4. The fusion protein according to claim 2 wherein said second fusion partner comprises all or part of an immunoglobulin constant heavy chain or immunoglobulin constant light chain, or both.
5. The fusion protein according to claim 1 wherein said first fusion partner sequence is the heavy chain sequence of: amino acids 21-50, 56-71, 88-119, and 131-141 of SEQ ID NO:12.
6. The fusion protein according to claim 1 wherein said first fusion partner sequence is the light chain sequence of: amino acids 20-42, 58-72, 80- 111, and 121 -131 of SEQ ID NO: 14.
7. The fusion protein according to claim 1 wherein said amino acid sequences of the complementarity determining regions for the heavy chain are:
(a) ThrSerGlyMetGlyValSer: SEQ ID NO:22, (b) HisIleTyrTrpAspAspAspLysArgTyrAsnPro-SerLeuLysSer: SEQ ID NO:24, or (c) ArgGluThrValPheTyrTrpPheAspVal: SEQ ID NO:26.
(a) ThrSerGlyMetGlyValSer: SEQ ID NO:22, (b) HisIleTyrTrpAspAspAspLysArgTyrAsnPro-SerLeuLysSer: SEQ ID NO:24, or (c) ArgGluThrValPheTyrTrpPheAspVal: SEQ ID NO:26.
8. The fusion protein according to claim 1 wherein said amino acid sequences of the complementarity determining regions for the light chain are:
(a) LeuAlaSerGlnSerValAspTyrAspGlyAspSerTyrMetAsn: SEQ ID
NO:16, (b) AlaAlaSerAsnLeuGluSer: SEQ ID NO:18, or (c) GlnGlnSerAsnGluAspProProArg: SEQ ID NO:28.
(a) LeuAlaSerGlnSerValAspTyrAspGlyAspSerTyrMetAsn: SEQ ID
NO:16, (b) AlaAlaSerAsnLeuGluSer: SEQ ID NO:18, or (c) GlnGlnSerAsnGluAspProProArg: SEQ ID NO:28.
9. The fusion protein according to claim 1 wherein said amino acid sequences of the complementarity determining regions for the light chain are:
(a) LysAlaSerGlnSerValAspTyrAspGlyAspSerTyrMetAsn: SEQ ID
NO: 16, (b) AlaAlaSerAsnLeuGluSer: SEQ ID NO:18, or (c) GlnGlnSerAsnGluAspProProThr: SEQ ID NO:20.
(a) LysAlaSerGlnSerValAspTyrAspGlyAspSerTyrMetAsn: SEQ ID
NO: 16, (b) AlaAlaSerAsnLeuGluSer: SEQ ID NO:18, or (c) GlnGlnSerAsnGluAspProProThr: SEQ ID NO:20.
10. An immunoglobulin heavy chain complementarity determining region (CDR), the amino acid sequence of which is selected from the group consisting of:
(a) ThrSerGlyMetGlyValSer: SEQ ID NO:22, (b) HisIleTyrTrpAspAspAspLysArgTyrAsnPro-SerLeuLysSer: SEQ ID NO:24, and (c) ArgGluThrValPheTyrTrpPheAspVal: SEQ ID NO:26.
(a) ThrSerGlyMetGlyValSer: SEQ ID NO:22, (b) HisIleTyrTrpAspAspAspLysArgTyrAsnPro-SerLeuLysSer: SEQ ID NO:24, and (c) ArgGluThrValPheTyrTrpPheAspVal: SEQ ID NO:26.
11. An immunoglobulin light chain complementarity determining region (CDR), the amino acid sequence of which is selected from the group consisting of:
(a) LeuAlaSerGlnSerValAspTyrAspGlyAspSerTyrMetAsn: SEQ ID
NO:16, (b) AlaAlaSerAsnLeuGluSer: SEQ ID NO: 18, (c) GlnGlnSerAsnGluAspProProArg: SEQ ID NO:28; and (d) GlnGlnSerAsnGluAspProProThr: SEQ ID NO:20.
(a) LeuAlaSerGlnSerValAspTyrAspGlyAspSerTyrMetAsn: SEQ ID
NO:16, (b) AlaAlaSerAsnLeuGluSer: SEQ ID NO: 18, (c) GlnGlnSerAsnGluAspProProArg: SEQ ID NO:28; and (d) GlnGlnSerAsnGluAspProProThr: SEQ ID NO:20.
12. A nucleic acid molecule encoding an immunoglobulin heavy chain complementarity deterrnining region (CDR), the sequence of which is selected from the group consisting of:
(a) ACT TCT GGT ATG GGT GTG AGC: SEQ ID NO:21, (b) CAC ATT TAC TGG GAT GAT GAC AAG CGC TAT
AACCCATCCCTGAAGAGC: SEQ ID NO:23, (c) AGA GAG ACT GTG TTC TAC TGG TAC TTC GAT
GTC: SEQ ID NO:25, (d) ACC TCC GGT ATG GGT GTT TCC: SEQ ID NO: 54, (e) CAC ATC TAC TGG GAC GAC GAC AAA CGT TAC AAC CCG
AGC CTG AAA TCC: SEQ ID NO: 55, and (f) CGC GAA ACC GTT TTC TAC TGG TAC TTC GAC GTT: SEQ
ID NO:56.
(a) ACT TCT GGT ATG GGT GTG AGC: SEQ ID NO:21, (b) CAC ATT TAC TGG GAT GAT GAC AAG CGC TAT
AACCCATCCCTGAAGAGC: SEQ ID NO:23, (c) AGA GAG ACT GTG TTC TAC TGG TAC TTC GAT
GTC: SEQ ID NO:25, (d) ACC TCC GGT ATG GGT GTT TCC: SEQ ID NO: 54, (e) CAC ATC TAC TGG GAC GAC GAC AAA CGT TAC AAC CCG
AGC CTG AAA TCC: SEQ ID NO: 55, and (f) CGC GAA ACC GTT TTC TAC TGG TAC TTC GAC GTT: SEQ
ID NO:56.
13. A nucleic acid molecule encoding an immunoglobulin light chain complementarity determining region (CDR), the sequence of which is selected fromthe group consisting of:
(a) AAG GCC AGC CAA AGT GTT GAT TAT GAT GGT
GAT AGT TAT ATG AAC: SEQ ID NO:15, (b) AAG GCC TCC CAA AGT GTT GAT TAT GAT GGT GAT AGT
TAT ATG AAC: SEQ ID NO: 53, (c) GCT GCA TCC AAT CTA GAA TCT: SEQ ID NO:17, (d) CAG CAA AGT AAT GAG GAT CCT CCG ACG: SEQ ID N 0:19, and (e) CAG CAA AGT AAT GAG GAT CCT CCG AGG: SEQ ID NO:27.
(a) AAG GCC AGC CAA AGT GTT GAT TAT GAT GGT
GAT AGT TAT ATG AAC: SEQ ID NO:15, (b) AAG GCC TCC CAA AGT GTT GAT TAT GAT GGT GAT AGT
TAT ATG AAC: SEQ ID NO: 53, (c) GCT GCA TCC AAT CTA GAA TCT: SEQ ID NO:17, (d) CAG CAA AGT AAT GAG GAT CCT CCG ACG: SEQ ID N 0:19, and (e) CAG CAA AGT AAT GAG GAT CCT CCG AGG: SEQ ID NO:27.
14. A humanized antibody comprising a heavy chain and a light chain, said antibody characterized by a dissociation constant equal to or less than about 2 x 10-10 M for human ILA, wherein the framework regions of said heavy and light chains are derived from at least one selected human antibody and the amino acid sequences of the complementarity determining regions of each said chain are derived from a non-human neutralizing monoclonal antibody specific for human IL4characterized by a dissociation constant equal to or less than about 2 x 10-10 M for human IIA.
15. The antibody according to claim 14 wherein said antibody is optionally linked to an effector agent selected from the group consisting of a non-protein carrier molecule, polystyrene, and plastic beads.
16. A chimeric antibody comprising a heavy chain and a light chain, said antibody characterized by a dissociation constant equal to or less than about 2 x 10-10 M for human IL4, wherein the amino acid sequences of the complementarity determining regions of said heavy chain and said light chain are derived from a non-human neutralizing monoclonal antibody specific for human IL4 characterized by adissociation constant equal to or less than about 2 x 10-10 M for human ILA.
17. A pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier.
18. A method of treating allergies and other conditions associated with excess IgE production in a human comprising the step of administering to said human in need thereof an effective amount of the fusion protein of claim 1.
19. An isolated nucleic acid sequence which is selected from the group consisting of:
(a) a nucleic acid sequence encoding the fusion protein of claim 1;
(b) a nucleic acid sequence complementary to (a);
(c) a nucleic acid sequence of 18 or more nucleotides capable of hybridizing to (a) or (b) under stringent conditions; and (d) a fragment or analog of (a), (b), or (c) which encodes a protein characterized by having specificity for human interleukin-4;
wherein said sequence optionally contains a restriction site.
(a) a nucleic acid sequence encoding the fusion protein of claim 1;
(b) a nucleic acid sequence complementary to (a);
(c) a nucleic acid sequence of 18 or more nucleotides capable of hybridizing to (a) or (b) under stringent conditions; and (d) a fragment or analog of (a), (b), or (c) which encodes a protein characterized by having specificity for human interleukin-4;
wherein said sequence optionally contains a restriction site.
20. The isolated nucleic acid sequence according to claim 19, wherein the sequence encoding the fusion protein comprises the nucleic acid sequence of Fig. 5,SEQ ID NO:13.
21. The isolated nucleic acid sequence according to claim 19, wherein the sequence encoding the fusion protein comprises the nucleic acid sequence of Fig. 4, SEQ ID NO:11.
22. An isolated nucleic acid sequence which is selected from the group consisting of:
(a) a nucleic acid sequence encoding a complementarity determining region (CDR) wherein said CDR is obtained from a neutralizing murinemonoclonal antibody specific for human interleukin-4 and having a dissociation constant equal to or less than about 2 x 10-10M;
(b) a nucleic acid sequence complementary to (a);
(c) a nucleic acid sequence of 18 or more nucleotides capable of hybridizing under stringment conditions to (a) or (b); and (d) a fragment or analog of (a), (b) or (c) which encodes a protein characterized by having specificity for human interleukin-4.
(a) a nucleic acid sequence encoding a complementarity determining region (CDR) wherein said CDR is obtained from a neutralizing murinemonoclonal antibody specific for human interleukin-4 and having a dissociation constant equal to or less than about 2 x 10-10M;
(b) a nucleic acid sequence complementary to (a);
(c) a nucleic acid sequence of 18 or more nucleotides capable of hybridizing under stringment conditions to (a) or (b); and (d) a fragment or analog of (a), (b) or (c) which encodes a protein characterized by having specificity for human interleukin-4.
23. The isolated nucleic acid sequence according to claim 22, wherein said sequence is selected from the group of heavy chain complementarity determining region-encoding sequences consisting of:
(a) ACT TCT GGT ATG GGT GTG AGC: SEQ ID NO:21, (b) CAC ATT TAC TGG GAT GAT GAC AAG CGC TAT
AAC CCA TCC CTG AAG AGC: SEQ ID NO:23, (c) AGA GAG ACT GTG TTC TAC TGG TAC TTC GAT
GTC: SEQ ID NO:25, (d) ACC TCC GGT ATG GGT GTT TCC: SEQ ID NO: 54, (e) CAC ATC TAC TGG GAC GAC GAC AAA CGT TAC AAC CCG
AGC CTG AAA TCC: SEQ ID NO: 55, and (f) CGC GAA ACC GTT TTC TAC TGG TAC TTC GAC GTT:
SEQ ID NO: 56.
(a) ACT TCT GGT ATG GGT GTG AGC: SEQ ID NO:21, (b) CAC ATT TAC TGG GAT GAT GAC AAG CGC TAT
AAC CCA TCC CTG AAG AGC: SEQ ID NO:23, (c) AGA GAG ACT GTG TTC TAC TGG TAC TTC GAT
GTC: SEQ ID NO:25, (d) ACC TCC GGT ATG GGT GTT TCC: SEQ ID NO: 54, (e) CAC ATC TAC TGG GAC GAC GAC AAA CGT TAC AAC CCG
AGC CTG AAA TCC: SEQ ID NO: 55, and (f) CGC GAA ACC GTT TTC TAC TGG TAC TTC GAC GTT:
SEQ ID NO: 56.
24. The isolated nucleic acid sequence according to claim 22, wherein said sequence is selected from the group of light chain complementarity determining region-encoding sequences consisting of:
(a) AAG GCC AGC CAA AGT GTT GAT TAT GAT GGT
GAT AGT TAT ATG AAC: SEQ ID NO: 15, (b) AAG GCC TCC CAA AGT GTT GAT TAT GAT GGT GAT AGT
TAT ATG AAC: SEQ ID NO: 53, (c) GCT GCA TCC AAT CTA GAA TCT: SEQ ID NO:17, (d) CAG CAA AGT AAT GAG GAT CCT CCG ACG: SEQ ID NO: 19, and (e) CAG CAA AGT AAT GAG GAT CCT CCG AGG: SEQ ID NO:27.
(a) AAG GCC AGC CAA AGT GTT GAT TAT GAT GGT
GAT AGT TAT ATG AAC: SEQ ID NO: 15, (b) AAG GCC TCC CAA AGT GTT GAT TAT GAT GGT GAT AGT
TAT ATG AAC: SEQ ID NO: 53, (c) GCT GCA TCC AAT CTA GAA TCT: SEQ ID NO:17, (d) CAG CAA AGT AAT GAG GAT CCT CCG ACG: SEQ ID NO: 19, and (e) CAG CAA AGT AAT GAG GAT CCT CCG AGG: SEQ ID NO:27.
25. A recombinant plasmid comprising the nucleic acid sequence of claim 19.
26. A recombinant plasmid comprising the nucleic acid sequence of claim 22.
27. A host cell transfected with the recombinant plasmid of claim 25.
28. A host cell transfected with the recombinant plasmid of claim 26.
29. A process for producing a humanized antibody specific for human interleukin-4 comprising culturing a cell line transfected with the recombinant plasmid of claim 25 under the control of selected regulatory sequences capable of directing the expression thereof in said cells.
30. A method for diagnosing allergies and other conditions associated with excess immunoglobulin E production in a human which comprises contacting a sample of biological fluid with a high titer monoclonal antibody for human IL4 and assaying for the occurrence of binding between said monoclonal antibody and human interleukin 4.
31. A method for screening monoclonal antibodies which have ahigh titer for human interleukin 4 which comprises:
a) preparing a hybridoma cell line characterized by secretion of a monoclonal antibody to human interleukin 4; and b) screening said hybridoma cell line with aldehyde-coupled human interleukin-4 or biotinylated human interleukin-4.
a) preparing a hybridoma cell line characterized by secretion of a monoclonal antibody to human interleukin 4; and b) screening said hybridoma cell line with aldehyde-coupled human interleukin-4 or biotinylated human interleukin-4.
32. A neutralizing monoclonal antibody having a high titer for human interleukin-4, a Fab fragment or a F(ab')2 fragment thereof, produced by screening a library of hydridoma products with aldehyde-coupled human interleukin-4 or biotinylated human interleukin-4.
33. A rodent neutralizing monoclonal antibody specific for human interleukin-4 and having a binding affinity characterized by a dissociation constant equal to or less than about 2 x 10-10 M.
34. The monoclonal antibody according to claim 33 wherein said rodent is a mouse.
35. The monoclonal antibody according to claim 34, which comprises the light chain amino acid sequence of SEQ ID NO: 2, and the heavy chain amino acid sequence of SEQ ID NO: 4.
36. The monoclonal antibody according to claim 33, wherein said rodent is a rat.
37. The monoclonal antibody according to claim 36 having the identifying characteristics of 6A1.
38. A hybridoma having the identifying characteristics of cell line 3426A11C1B9.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11736693A | 1993-09-07 | 1993-09-07 | |
| US08/117,366 | 1993-09-07 | ||
| US13678393A | 1993-10-14 | 1993-10-14 | |
| US08/136,783 | 1993-10-14 | ||
| PCT/US1994/010308 WO1995007301A1 (en) | 1993-09-07 | 1994-09-07 | Recombinant il4 antibodies useful in treatment of il4 mediated disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2171336A1 true CA2171336A1 (en) | 1995-03-16 |
| CA2171336C CA2171336C (en) | 2011-06-21 |
Family
ID=26815208
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2171336A Expired - Fee Related CA2171336C (en) | 1993-09-07 | 1994-09-07 | Recombinant il4 antibodies useful in treatment of il4 mediated disorders |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0730609B1 (en) |
| JP (4) | JPH09502708A (en) |
| KR (1) | KR100362340B1 (en) |
| CN (2) | CN1473854A (en) |
| AP (1) | AP583A (en) |
| AT (1) | ATE286510T1 (en) |
| AU (1) | AU695726B2 (en) |
| BG (1) | BG63549B1 (en) |
| BR (1) | BR9407575A (en) |
| CA (1) | CA2171336C (en) |
| CZ (1) | CZ295928B6 (en) |
| DE (1) | DE69434223T2 (en) |
| ES (1) | ES2236693T3 (en) |
| FI (1) | FI119733B (en) |
| HU (1) | HU222041B1 (en) |
| NO (1) | NO960956L (en) |
| NZ (1) | NZ274338A (en) |
| PL (1) | PL180125B1 (en) |
| SK (1) | SK285556B6 (en) |
| UA (1) | UA48940C2 (en) |
| WO (1) | WO1995007301A1 (en) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
| US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
| US6768004B2 (en) * | 2001-01-11 | 2004-07-27 | Mueller Sybille | Nucleotide sequences encoding variable regions of heavy and light chains of monoclonal antibody 1F7, an anti-idiotypic antibody reactive with anti-HIV antibodies |
| MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| TWI374893B (en) * | 2003-05-30 | 2012-10-21 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| DE602005018325D1 (en) | 2004-02-19 | 2010-01-28 | Genentech Inc | ANTIBODIES WITH CORRECTED CDR |
| AR050044A1 (en) | 2004-08-03 | 2006-09-20 | Novartis Ag | IL-4 SPECIFIC ANTIBODY |
| AR052051A1 (en) | 2004-12-15 | 2007-02-28 | Neuralab Ltd | AB HUMANIZED ANTIBODIES USED TO IMPROVE COGNITION |
| US20100297110A1 (en) * | 2006-03-22 | 2010-11-25 | Apogenix Gmbh | Antibody specific for human il-4 for the treatment of cancer |
| US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
| ATE520032T1 (en) | 2006-06-21 | 2011-08-15 | Apogenix Gmbh | DIFFERENTIAL CYTOKINE EXPRESSION IN HUMAN CANCER |
| US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
| JP4971872B2 (en) | 2007-05-23 | 2012-07-11 | 株式会社トプコン | Fundus observation apparatus and program for controlling the same |
| PT2182983E (en) | 2007-07-27 | 2014-09-01 | Janssen Alzheimer Immunotherap | Treatment of amyloidogenic diseases with humanised anti-abeta antibodies |
| EP2050764A1 (en) | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| JO3076B1 (en) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | Immunotherapy regimes dependent on apoe status |
| JP5324839B2 (en) | 2008-06-19 | 2013-10-23 | 株式会社トプコン | Optical image measuring device |
| US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| CN102294024B (en) * | 2011-01-17 | 2013-03-13 | 广东现代农业集团研究院有限公司 | Polypeptide vaccine and preparation method thereof |
| EP3514181A1 (en) * | 2015-02-24 | 2019-07-24 | Academia Sinica | A phage-displayed single-chain variable fragment library and antibodies selected therefrom |
| CN112625129B (en) * | 2020-11-26 | 2022-05-20 | 江苏荃信生物医药股份有限公司 | Anti-human interleukin 23, kit comprising same and detection method thereof |
| CN114891111A (en) * | 2020-12-31 | 2022-08-12 | 中元汇吉生物技术股份有限公司 | Protein specifically binding to human IgG4 and application thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5041381A (en) * | 1986-07-03 | 1991-08-20 | Schering Corporation | Monoclonal antibodies against human interleukin-4 and hybridomas producing the same |
| JP2646007B2 (en) * | 1988-01-30 | 1997-08-25 | 財団法人 化学及血清療法研究所 | Gene fragment encoding anti-HIV antibody variable region, anti-HIV chimeric antibody expressed using the same, and method for producing the same |
| EP0365209A3 (en) * | 1988-10-17 | 1990-07-25 | Becton, Dickinson and Company | Anti-leu 3a amino acid sequence |
| IL162181A (en) * | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| JPH07119238B2 (en) * | 1989-12-18 | 1995-12-20 | 小野薬品工業株式会社 | Monoclonal antibody against human interleukin-4 and method of using the antibody |
| AU639754B2 (en) * | 1989-12-20 | 1993-08-05 | Schering Corporation | Antibody antagonists of human interleukin-4 |
| JPH04141095A (en) * | 1990-10-02 | 1992-05-14 | Chemo Sero Therapeut Res Inst | Hiv-resistant recombined modified antibody and method for preparing modified antibody |
| JPH07502901A (en) * | 1992-02-19 | 1995-03-30 | シェリング・コーポレーション | Cloning and expression of humanized monoclonal antibodies against human interleukin-4 |
| JPH06269663A (en) * | 1993-03-17 | 1994-09-27 | Toyobo Co Ltd | Cd4 positive cell capturing material |
| DE60025364T2 (en) * | 1999-07-30 | 2006-08-03 | Battelle Memorial Institute, Richland | CERAMIC COMPOUND MATERIAL AND COMPOUND PROCESS |
-
1994
- 1994-09-07 AU AU78340/94A patent/AU695726B2/en not_active Ceased
- 1994-09-07 DE DE69434223T patent/DE69434223T2/en not_active Expired - Lifetime
- 1994-09-07 EP EP94929191A patent/EP0730609B1/en not_active Expired - Lifetime
- 1994-09-07 ES ES94929191T patent/ES2236693T3/en not_active Expired - Lifetime
- 1994-09-07 NZ NZ274338A patent/NZ274338A/en not_active IP Right Cessation
- 1994-09-07 UA UA96041300A patent/UA48940C2/en unknown
- 1994-09-07 SK SK333-96A patent/SK285556B6/en not_active IP Right Cessation
- 1994-09-07 CN CNA031043178A patent/CN1473854A/en active Pending
- 1994-09-07 CN CN94193929A patent/CN1105728C/en not_active Expired - Fee Related
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- 1994-09-07 AP APAP/P/1996/000782A patent/AP583A/en active
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- 1994-09-07 HU HU9600616A patent/HU222041B1/en not_active IP Right Cessation
- 1994-09-07 WO PCT/US1994/010308 patent/WO1995007301A1/en active IP Right Grant
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- 1994-09-07 JP JP7508835A patent/JPH09502708A/en active Pending
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1996
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2006
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2009
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